Elsevier

Metabolism

Volume 105, April 2020, 154138
Metabolism

Commentary
Time trends and predictors of hypovitaminosis D across the life course: 2009–2016

https://doi.org/10.1016/j.metabol.2020.154138Get rights and content

Highlights

  • There was a significant steady increase in mean serum 25OHD levels from 2009 to 2016.

  • The average prevalence of low 25OHD (<20 ng/ml) was 39% across all years.

  • Young age, male sex, winter and hospitalization predict low 25OHD in adults/elderly.

  • Older age, female sex, winter and hospitalization predict low 25OHD in children.

  • In adults and elderly, PTH levels plateaued at a serum 25OHD level of 26 ng/ml.

Abstract

Purpose

We investigated prevalence, determinants, seasonal changes, and time trends in hypovitaminosis D. We derived a desirable serum 25-hydroxy-vitamin D (25OHD) level in adults/elderly by evaluating the 25OHD-parathyroid hormone (PTH) exponential relationship.

Methods

We analyzed serum 25OHD data from a large laboratory database (N = 151,705), from a major academic medical center in Lebanon, from 2009 to 2016. We used cross calibration formulas to convert measured 25OHD levels to LC-MS/MS equivalents based on our external quality assurance protocols.

Results

6% of the population were children (mean age 11 ± 5 years, 56% girls), 68% were adults (44 ± 13 years, 71% women), and 25% were elderly (74 ± 6 years, 59% women). The prevalence of hypovitaminosis D, in the entire population, was 39%, 29% and 23% at 25OHD cutoffs of 20 ng/ml, 15 ng/ml, and 12 ng/ml, respectively, across all years. Using multivariate analysis, predictors of 25OHD levels below 12, 15 and 20 ng/ml were younger age, male sex, winter months, and inpatient status both in adults and elderly. In children, older age, female sex, winter months, and inpatient status, predicted levels below 15 ng/ml and 20 ng/ml, but only older age, female sex, and winter months predicted levels below 12 ng/ml. There was a significant steady annual increase in 25OHD levels between 2009 and 2016 of 0.9 ng/ml/year (95% CI: 0.7, 1.0) in children, 1.2 ng/ml/year (1.2, 1.3) in adults and 2.6 ng/ml/year (2.6, 2.8) in the elderly. Using best fit non-linear regression models, on a subset of adults and elderly in whom concomitant 25OHD and PTH data was available (N = 4025), PTH levels plateaued at a serum 25OHD level of 26.1 ng/ml.

Conclusion

Secular increase in serum 25OHD levels is observed in Lebanon, but hypovitaminosis D is still prevalent. Our data provides basis for a desirable 25OHD level above 26 ng/ml in adult and elderly Lebanese individuals.

Introduction

Vitamin D is obtained both from diet and sun exposure, with the most important source being exposure to Ultraviolet B radiation [1,2]. Deficiency in vitamin D has been linked to skeletal abnormalities, rickets and growth problems in children, and to osteomalacia, osteopenia, osteoporosis and skeletal fractures in adults [[3], [4], [5]]. It is also associated with extra-skeletal diseases including autoimmunity, cancer, respiratory diseases and neurologic disorders [6]. Serum 25-hydroxyvitamin D (25OHD) level is currently the best indicator of body vitamin D stores and is thus the marker of interest [2,4,5,7].

There are wide geographic variations in hypovitaminosis D, mostly explained by differences in environmental and, to a lesser extent, genetic factors, in addition to differences in assays used to measure serum 25OHD levels and in the cut-offs selected [4,8,9].

Hypovitaminosis D is common in Eastern and Southern Europe [1,5], Asia [4,8,10] and in the Middle East [1,2,4,5,8,10]. In Europe, specific risk groups include infants and children up to 3 years of age, pregnant women, older persons and non-western immigrants [1]. In a multinational study of 18 countries with various latitudes, conducted on women with osteoporosis, the lowest serum 25OHD levels were recorded in the Middle East [5]. In Lebanon, despite plentiful sunshine, with over 300 sunny days per year, our group reported a high prevalence of 25OHD levels below 20 ng/ml, between the years 2000–2004 (58% in pediatrics, 44% in adults and 41% in elderly) and 2007–2008 (62%, 60% and 62%, respectively) [11]. Predictors of high serum 25OHD level in Lebanon included male sex in children, female sex in adults and elderly, and having measurements taken in summer or fall season [11]. Other known predictors include clothing type, time spent outdoors, pollution and genetic factors [2,5,12].

Interestingly, a clear increase in serum 25OHD levels was noted in the United States after 2007 and coincided with an increase in vitamin D supplementation [13]. Our group observed a similar consistent rise in vitamin D levels in Lebanon between 2000–2004 and 2007–2008, in both sexes, and across all age groups [11].

Great controversy exists with regards to the optimal serum 25OHD level for bone health [8,14,15]. Most guidelines, including the Institute of Medicine (IOM) guidelines reported little or no additional benefit with levels >20 ng/ml [[15], [16], [17]]. However, a level of 30 ng/ml or greater was recommended by the Endocrine Society [18], the International Osteoporosis Foundation [10], the National Osteoporosis Foundation [19] and the American Geriatric Society [20]. Parathyroid hormone (PTH) decline with serum 25OHD increments was used as a surrogate for bone health, to determine the target serum 25OHD levels in different adult and elderly populations [11,21].

The objectives of this follow up study [11] were to assess the prevalence of hypovitaminosis D, define its determinants, and investigate time trends in serum 25OHD levels in Lebanon. We also evaluated the 25OHD-PTH relationship to derive a desirable mean 25OHD in the non-pediatric population.

Section snippets

Study population

We retrieved anonymous demographic and laboratory data of patients, from all age groups, who underwent serum 25OHD measurements at the American University of Beirut -Medical Center (AUB-MC), between January 1st, 2009 and July 19th, 2016, using the digitized database of the Clinical Pathology and Laboratory Medicine department.

In addition to serum 25OHD levels, we collected information on patients' serum calcium (Ca), phosphorus (PO4), alkaline phosphatase (ALKsingle bondP), PTH, and creatinine (Cr)

Population demographics

The total number of patients who underwent serum 25OHD assessment during our study period was 198,811. After applying the exclusion criteria described in Methods and omitting patients with repeated serum 25OHD measures over consecutive years, we analyzed data from 151,705 patients: 4.6% in 2009, 8.3% in 2010, 13.0% in 2011, 14.3% in 2012, 15.0% in 2013, 16.1% in 2014, 18.1% in 2015, and 10.8% in 2016. Of the total, 6% were children, mean age 11 ± 5 years, 68% were adults, mean age

Discussion

To our knowledge, this is the largest study to investigate hypovitaminosis D and time trends in the Middle East and North Africa (MENA) region, over a large time span, and follows on a similarly conducted study [11]. There was significant increase in mean serum 25OHD levels over an 8 year time span. Our population had a female predominance, and serum 25OHD measurements were mainly performed in an outpatient setting. Overall, the prevalence of low 25OHD levels was 39% at a cutoff of 20 ng/ml,

Authors contribution

Randa K. Saad: Conceptualization, Methodology, Validation, Formal Analysis, Investigating, Data Curation, Writing - Original Draft, Writing - Review & Editing, Visualization. Vanessa C. Akiki: Conceptualization, Methodology, Writing - Original Draft, Writing - Review & Editing. Maya Rahme: Investigation, Data Curation. Mariam Assaad: Investigation, Data Curation. Sara Ajjour: Investigation, Data Curation. Ghada El-Hajj Fuleihan: Conceptualization, Methodology, Validation, Resources, Writing -

Funding

This research received funding from the Medical Practice Plan (MPP) at the American University of Beirut-Medical Center Beirut, Lebanon.

Declaration of competing interest

None. All authors have approved the final article.

Acknowledgments

RS received training under the Scholars in HeAlth Research Program (SHARP), Fogarty International Center and Office of Dietary Supplements of the National Institutes of Health (NIH) under Award Number D43 TW009118. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors thank Dr. Laila Al Shaar for her help in finalizing the equation and fitting the curve to define the 25OHD inflection point.

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    Randa K. Saad and Vanessa C. Akiki contributed to the manuscript equally.

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